Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance is accepted as the underlying fundamental defect that predates and ultimately leads to the development of type 2 (adult onset) diabetes mellitus in the general non-human immunodeficiency virus (HIV)-infected population. Insulin resistance is also a major component of the metabolic syndrome that, in association with other factors such as hypertension, hypercholesterolemia, and central obesity, defines a pre-diabetic atherogenic state that leads to adverse cardiovascular events. Growing evidence now suggests that mitochondrial dysfunction in skeletal muscle may be the mechanism whereby insulin resistance is induced. The prevalence of insulin resistance, glucose intolerance, and diabetes in the HIV-infected population has dramatically increased following the common use of highly active antiretroviral therapy (HAART). The development of insulin resistance in the HIV-infected population is likely to be multifactorial reflecting genetic predisposition, direct and indirect effects of both the protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NRTI) class of antiretroviral therapy, and a possible contribution from chronic inflammatory changes induced by HIV. Indirect effects of antiretroviral therapy on insulin resistance may be mediated through both the visceral adiposity and peripheral fat depletion components of lipodystrophy as well as through fatty infiltration in liver and muscle. Based on current knowledge, mitochondrial dysfunction can be hypothesized to play a key role in each of these components.
 ...
PMID:Insulin resistance in the HIV-infected population: the potential role of mitochondrial dysfunction. 1618 Nov 44

Although it is well accepted that treatment with some nucleoside reverse transcriptase inhibitors modifies both fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examined whether a decrease in oxidative capacity, induced by a chronic oral administration of 3'-azido-3'-deoxythymidine (AZT) in rats, could be associated with an alteration of the lipogenic capacity of white adipose tissues. The impact of obesity as a factor was then evaluated. Results showed that AZT treatment induced differential effects depending on anatomical localization. Indeed, in the inguinal adipose tissue, the specific activities of cytochrome c oxidase and fatty acid synthase, two rate-controlling enzymes in energy and lipogenic metabolisms, respectively, both decreased under AZT treatment, thus leading to a lowered cell lipid accumulation. Moreover, the AMP-activated protein kinase phosphorylation level tended to increase, thus implying that AZT causes an energy imbalance. Furthermore, the inguinal tissue of obese rats presented a sensitivity to AZT treatment that was higher than that of lean rats. In contrast, for epididymal tissue, no significant change in all these parameters could be detected under AZT treatment, regardless of the nutritional status of the animals. Taken together, these data demonstrate differential effects of AZT on subcutaneous adipose tissue and visceral white adipose tissue. It could be considered that the chronic decreases in energy and lipogenic metabolism of inguinal adipocyte, consecutive to AZT treatment, may lead, in the long term, to adipose tissue atrophy.
 ...
PMID:Site-specific reduction of oxidative and lipid metabolism in adipose tissue of 3'-azido-3'-deoxythymidine-treated rats. 1715 34

In order to investigate the effects of simvastatin on secretion and mRNA expression of interleukin-6 (IL-6) and adiponectin in 3T3-L1 adipocytes, mouse 3T3-L1 adipocytes were stimulated with lipopolysaccharide (LPS). Production and mRNA expression of IL-6 and adiponectin in 3T3-L1 adipocytes were measured using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The results showed that simvastatin could significantly suppress LPS-induced IL-6 production and mRNA expression in adipocytes (P<0.05), but increase the LPS-induced adiponectin secretion and mRNA expression in a dose-dependent manner (P<0.05). It was suggested that simvastatin could exert beneficial effects on prevention of obesity-induced metabolic changes in adipocytes.
 ...
PMID:Effect of simvastatin on IL-6 and adiponectin secretion and mRNA expression in 3T3-L1 adipocytes. 1764 34

To determine if tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). IL-6 gene expression is influenced by amount and source of dietary fat, 30 weanling female rats were randomly assigned to a moderate-fat soybean oil (MFS; 22% of total energy fed as fat), high-fat (HF) soybean oil (HFS; 39% of total energy fed as fat), or HF tallow (HFT; 39% of total energy fed as fat) diet treatments. Oral glucose tolerance tests (OGTT) were conducted serially over 10 weeks of treatment. HFT and HFS rats gained more weight and had greater body fat than the MFS rats fed similar amounts of energy. Both groups of HF-fed rats had greater (P<.05) insulin resistance (homeostasis model assessment) than MFS-fed rats. TNF-alpha mRNA abundance quantified by real-time reverse transcriptase-polymerase chain reaction was greater (P<.05) in liver and lower (P<.05) in adipose tissue in HFT compared to HFS and MFS rats. There were positive correlations (P<.05) between hepatic TNF-alpha mRNA and insulin resistance, and negative correlations between insulin sensitivity and hepatic TNF-alpha mRNA and hepatic IL-6 mRNA. During Week 3 and Week 6 OGTTs, hyperinsulinemic responses were observed in the HFT group, after which, on Week 9, insulin secretion was diminished in response to the OGTT, suggesting impaired pancreatic insulin secretion. HFS rats exhibited insulin resistance on Week 9 OGTT. In summary, an HFT diet fed to growing female rats caused insulin resistance associated with increased hepatic TNF-alpha mRNA leading to pancreatic insufficiency. Early-onset insulin resistance related to the inflammatory process in obesity is influenced by the amount and type of fat in the diet.
 ...
PMID:High-fat diets promote insulin resistance through cytokine gene expression in growing female rats. 1790 44

Hepatic acyl-coenzyme A synthetase (ACS), carnitine palmitoyltransferase-I (CPT-I) and acetyl coenzyme A carboxylase (ACC) are coenzymes associated with the genetic type of obesity in animal models. This paper reports the use of microchip electrophoresis (ME) with a laser-induced fluorescence (LIF) detector based on a reverse transcriptase-polymerase chain reaction (RT-PCR) to detect the amplified DNA fragments of these coenzymes (ACS, CPT-I and ACC) in the mRNA extracted from mice. DNA fragments ranging from 50 to 2652 bp were well resolved using this procedure with a running buffer (1x TBE), 0.5% polyvinylpyrrolidone (M(r) 1,000,000) as the coating gel and 0.7% polyethyleneoxide (M(r) 8,000,000) as the sieving gel at pH 8.30. The separation of the three RT-PCR products was achieved by ME in a single-run within 17 s using programmed field strength gradients (PFSG) (470 V cm(-1) for 9 s, 205.8 V cm(-1) for 2 s, 411.6 V cm(-1) for 4 s, 117.6 V cm(-1) for 2 s and 470.4V cm(-1) for 8 s). The ME-PFSG method was found to be 4 times faster than the method using a constant field and 138 times faster than slab gel electrophoresis. Moreover, the amplified RT-PCR products of the obesity-related coenzymes in C57BL/6J mice were analyzed using only sub-micro liter samples.
 ...
PMID:Ultra-fast simultaneous detection of obesity-related coenzymes in mice using microchip electrophoresis with a LIF detector. 1853 80

The objectives of this study were to identify potential alterations in gene expression of melanocortin-4 receptor (MC4-R), proopiomelanocortin (POMC), and Agouti-related protein (AgRP) in mouse hypothalamus under a chronic peripheral infusion of leptin or at early (8 weeks) and advanced (16 weeks) phases of diet-induced obesity. Control or diet-induced obesity mice (8 or 16 weeks of high-fat diet) were either treated or not treated with leptin. Metabolic features were analyzed and expression of the genes of interest was measured by quantitative reverse transcriptase-PCR (RT-qPCR) and western blot. We reported that in control mice, but not in obese mice, leptin infusion induced an increase in POMC mRNA level as well as in MC4-R mRNA level suggesting that leptin could act directly and/or through alpha-melanocyte-stimulating hormone (alpha-MSH). This hypothesis was reinforced after in vitro studies, using the mouse hypothalamic GT1-7 cell line, since both leptin and Norleucine(4), D-Phenylalanine(7)-alpha-MSH (NDP-alpha-MSH) treatments increased MC4-R expression. After 8 weeks of high-fat diet, nondiabetic obese mice became resistant to the central action of leptin and their hypothalamic content of POMC and AgRP mRNA were decreased without modification of MC4-R mRNA level. After 16 weeks of high-fat diet, mice exhibited more severe metabolic disorders with type 2 diabetes. Moreover, hypothalamic expression of MC4-R was highly increased. In conclusion, several alterations of the melanocortin system were found in obese mice that are probably consecutive to their central resistance to leptin. Moreover, when the metabolic status is highly degraded (with all characteristics of a type 2 diabetes), other regulatory mechanisms (independent of leptin) can also take place.
Obesity (Silver Spring) 2008 Aug
PMID:Leptin infusion and obesity in mouse cause alterations in the hypothalamic melanocortin system. 1855 Nov 22

Dietary supplementation with resveratrol may produce calorie restriction-like effects on metabolic and longevity endpoints in mice. In this study, we sought to determine whether resveratrol treatment elicited other hallmark changes associated with calorie restriction, namely bradycardia and decreased body temperature. We found that during short-term treatment, wild-type mice on a calorie-restricted diet experienced significant decreases in both heart rate and body temperature after only 1 day whereas those receiving resveratrol exhibited no such change after 1 wk. We also used ob/ob mice to study the effects of long-term treatment because previous studies had indicated the therapeutic value of resveratrol against the linked morbidities of obesity and diabetes. After 12 wk, resveratrol treatment had produced no changes in either heart rate or body temperature. Strikingly, and in contrast to previous findings, we found that resveratrol-treated mice had significantly reduced endurance in a treadmill test. Quantitative reverse transcriptase-polymerase chain reaction suggested that a proposed target of resveratrol, Sirt1, was activated in resveratrol-treated ob/ob mice. Thus, we conclude that the bradycardia and hypothermia associated with calorie restriction occur through mechanisms unaffected by the actions of resveratrol and that further studies are needed to examine the differential effects of resveratrol in a leptin-deficient background.
 ...
PMID:Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction. 1905 39

Emerging evidence indicates the potential involvement of ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, in low-grade inflammatory diseases such as obesity and atherosclerosis. The goal of the present study was to use cell culture models to investigate the influences of ghrelin and obestatin in processes participating in atherogenesis. We studied monocyte adhesion, monocyte chemoattractant protein-1, and adhesion molecule expression on endothelial cells as well as binding of oxidized low-density lipoprotein (LDL) and acetylated LDL to macrophages. Ghrelin treatment increased adhesion of calcein-labeled THP-1 monocytes to EA.hy 926 endothelial cells. Simultaneously, ghrelin increased the expression of intercellular adhesion molecule-1 measured by quantitative reverse transcriptase polymerase chain reaction. Tumor necrosis factor-alpha stimulation together with ghrelin treatment decreased both monocyte adhesion and vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1 expression and, together with obestatin treatment, decreased vascular cell adhesion molecule-1 expression. Finally, ghrelin and obestatin increased binding of oxidized LDL to thioglycollate-elicited mouse peritoneal macrophages. No changes were observed in the uptake of acetylated LDL by mouse J774.A1 macrophages after exposure to ghrelin or obestatin. In conclusion, we found 3 lines of in vitro evidence supporting proatherogenic properties of ghrelin in the early stages of the disease. However, in the presence of tumor necrosis factor-alpha stimulation, opposite effects of ghrelin were observed, suggesting that ghrelin may also have an anti-inflammatory role in the presence of increased inflammation, for example, during the more progressed phases of atherogenesis.
 ...
PMID:Ghrelin and obestatin modulate early atherogenic processes on cells: enhancement of monocyte adhesion and oxidized low-density lipoprotein binding. 1960 5

Dysregulation of the endocannabinoid system in the visceral adipose tissue (VAT) is associated with metabolic and cardiovascular complications of obesity. We studied perirenal VAT CB1 receptor expression in relation to anthropometry, VAT area and endocannabinoid levels, kidney microvascular damage (MVDa), and the presence of the CB1 gene A3813G variant, the frequency of which was also evaluated in a large population of obese-hypertensive (OH) patients with or without the metabolic syndrome (MetS). Perirenal VAT and kidney samples were obtained from 30 patients undergoing renal surgery. Total and perirenal VAT areas were determined by computed tomography. CB1 messenger RNA expression and endocannabinoid levels in perirenal VAT were determined by quantitative reverse transcriptase polymerase chain reaction and liquid chromatography-mass spectrometry, respectively. The MVDa was evaluated in healthy portions of kidney cortex. The A3813G alleles were identified by genotyping in these patients and in 280 nondiabetic OH patients (age <or=65 years). Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Perirenal VAT CB1 expression was 40% lower in patients with the A3813G polymorphism, and correlated positively with perirenal and total VAT area and with perirenal VAT levels of the endocannabinoid anandamide. A 2-fold higher CB1 expression was associated with MVDa. The OH patients with the A3813G allele had lower prevalence of MetS in both unadjusted and adjusted models. Genetics influence perirenal VAT CB1 expression and the prevalence of MetS in OH. Increased VAT is associated with increased perirenal VAT endocannabinoid tone, which in turn correlates with increased MVDa. Endocannabinoid overactivity might be involved in human visceral obesity and its renal complications.
 ...
PMID:Cannabinoid CB1 receptor expression in relation to visceral adipose depots, endocannabinoid levels, microvascular damage, and the presence of the Cnr1 A3813G variant in humans. 1991 70

Type 2 diabetes mellitus (T2D) is predicted by central obesity and circulating adipokines regulating inflammation. We hypothesized that visceral adipose tissue (VAT) in T2D expresses greater levels of proinflammatory molecules. Paired samples of subcutaneous (SAT) and VAT were excised at elective surgery (n = 16, 6 with T2D, n = 8 age- and gender- matched controls). Metabolic parameters were measured in the fasted state: body composition by dual-energy X-ray absorptiometry and insulin action by hyperinsulinemic-euglycemic clamp. Adipose tissue mRNA gene expression was measured by quantitative reverse transcriptase-PCR. Subjects with T2D had higher VAT expression of molecules regulating inflammation (tumor necrosis factor-alpha (TNFalpha), macrophage inflammatory protein (MIP), interleukin-8 (IL-8)). Fasting glucose related to VAT expression of TNFalpha, MIP, serum amyloid A (SAA), IL-1alpha, IL-1beta, IL-8, and IL-8 receptor. Abdominal fat mass was related to VAT expression of MIP, SAA, cAMP response element-binding protein (CREBP), IL-1beta, and IL-8. Insulin action related inversely to VAT complement C3 expression only. There were depot-specific differences in expression of serum T2D predictors: VAT expressed higher levels of complement C3; SAT expressed higher levels of retinol-binding protein-4 (RBP4), adiponectin, and leptin. In summary, VAT in T2D expresses higher levels of adipokines involved in inflammation. VAT expression of these molecules is related to fasting glucose and insulin action. Increased production of these proinflammatory molecules by VAT may explain the links observed between visceral obesity, insulin resistance, and diabetes risk.
Obesity (Silver Spring) 2010 May
PMID:Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. 2001 78


<< Previous 1 2 3 4 5 6 7 8 Next >>